線粒體鐵蛋白
位於5號人類染色體的基因
線粒體鐵蛋白是一種存在於線粒體內的亞鐵氧化酶。這種氧化還原酶與細胞質基質中的鐵蛋白在結構與功能上高度同源,兩者理化性質和結構極為相似,都具有鐵攝取、結合和儲存功能。人類的線粒體鐵蛋白由FTMT基因編碼。[2]
線粒體鐵蛋白 | |
---|---|
![]() | |
線粒體鐵蛋白的晶體結構[1] | |
識別 | |
符號 | MtF |
Entrez | 94033 |
HUGO | 17345 |
OMIM | 608847 |
RefSeq | NM_177478 |
UniProt | Q8N4E7 |
其他資料 | |
EC編號 | 1.16.3.1 |
基因座 | 5 q23.1 |
結構
人類線粒體鐵蛋白的前體蛋白由242個氨基酸殘基組成(其N端含有長度為57aa的引導鏈,用於將其帶入線粒體),相對分子質量約為30kDa,氨基酸序列與鐵蛋白重鏈和鐵蛋白輕鏈的同源性分別為79%和63%。成熟線粒體鐵蛋白蛋白由185個氨基酸殘基組成(一說由182個氨基酸殘基),相對分子質量約為22kDa。這些亞基可以相互結合形成一個擁有亞鐵氧化酶活性的蛋白質殼層,用於隔離有害的游離亞鐵離子。[3]儘管鐵蛋白的重鏈和線粒體鐵蛋白在晶體結構上極為相似,但前者是由重鏈和輕鏈組成的24-雜多聚體(heteropolymer),而後者是由24個相同亞基組成的純多聚體(homopolymer)。[4]線粒體鐵蛋白有67%是螺旋形的,拉氏構象圖顯示線粒體鐵蛋白大部分皆為α螺旋,只擁有少量β摺疊結構。
作用
線粒體鐵蛋白能在調節線粒體內的鐵穩態、保護線粒體免受氧化應激損傷,以及調節血紅素和鐵硫基團生物合成等方面發揮着重要作用。[5]在鐵粒幼紅細胞性貧血患者的幼紅細胞的血紅素合成酶有缺陷,為防止亞鐵離子不能參與血紅素合成而大量蓄積在線粒體內導致鐵負荷升高,線粒體鐵蛋白表達水平顯著上調,將過多的亞鐵離子氧化為高鐵離子儲存在線粒體鐵蛋白的殼狀結構中。環形鐵粒幼紅細胞是上述貧血類型的特異性標誌物,其核周線粒體內的多數鐵都以線粒體鐵蛋白的形式沉積。[6]在鐵粒幼紅細胞性貧血的病理狀況下,線粒體鐵蛋白高表達的幼紅細胞線粒體並無功能、壽命異常,說明線粒體鐵蛋白具有保護線粒體的重要作用。
參考文獻
- ^ PDB 1r03
- ^ Levi S, Corsi B, Bosisio M, Invernizzi R, Volz A, Sanford D, Arosio P, Drysdale J. A human mitochondrial ferritin encoded by an intronless gene (PDF). Journal of Biological Chemistry. July 6, 2001, 276 (27): 24437–24440 [2011-09-05]. PMID 11323407. doi:10.1074/jbc.C100141200. (原始內容 (PDF)存檔於2018-07-24) (英語).
- ^ Drysdale J, Arosio P, Invernizzi R, Cazzola M, Volz A, Corsi B, Biasiotto G, Levi S. Mitochondrial ferritin: a new player in iron metabolism. Blood Cells Mol. Dis. Nov–Dec 2002, 29 (3): 376–383. PMID 12547228. doi:10.1006/bcmd.2002.0577 (英語).
- ^ 孫蕾、袁粒星、高舉. 线粒体铁蛋白分子生物学及其与机体铁代谢的关系. International Journal of Blood Transfusion and Hematology. 2007, 30 (5): 447–449 (中文).
- ^ Langlois d'Estaintot B, Santambrogio P, Granier T, Gallois B, Chevalier JM, Précigoux G, Levi S, Arosio P. Crystal structure and biochemical properties of the human mitochondrial ferritin and its mutant Ser144Ala. Journal of Biological Chemistry. Jul 2, 2004, 340 (2): 277–293 [2011-09-05]. PMID 15201052. doi:10.1016/j.jmb.2004.04.036. (原始內容存檔於2016-04-07) (英語).
- ^ Cazzola M, Invernizzi R, Bergamaschi G, Levi S, Corsi B, Travaglino E, Rolandi V, Biasiotto G, Drysdale J, Arosio P. Mitochondrial ferritin expression in erythroid cells from patients with sideroblastic anemia. Blood. Mar 1, 2003, 101 (5): 1996–2000 [2011-09-06]. PMID 12406866. doi:10.1182/blood-2002-07-2006. (原始內容存檔於2019-11-02) (英語).
擴展閱讀
- Zanella I, Derosas M, Corrado M; et al. The effects of frataxin silencing in HeLa cells are rescued by the expression of human mitochondrial ferritin.. Biochim. Biophys. Acta. 2008, 1782 (2): 90–8. PMID 18160053. doi:10.1016/j.bbadis.2007.11.006.
- Wilkinson J, Di X, Schönig K; et al. Tissue-specific expression of ferritin H regulates cellular iron homoeostasis in vivo.. Biochem. J. 2006, 395 (3): 501–7. PMC 1462685 . PMID 16448386. doi:10.1042/BJ20060063.
- Iwasaki K, Mackenzie EL, Hailemariam K; et al. Hemin-mediated regulation of an antioxidant-responsive element of the human ferritin H gene and role of Ref-1 during erythroid differentiation of K562 cells.. Mol. Cell. Biol. 2006, 26 (7): 2845–56. PMC 1430308 . PMID 16537925. doi:10.1128/MCB.26.7.2845-2856.2006.
- Hasan MR, Tosha T, Theil EC. Ferritin contains less iron (59Fe) in cells when the protein pores are unfolded by mutation.. J. Biol. Chem. 2008, 283 (46): 31394–400. PMC 2581568 . PMID 18805796. doi:10.1074/jbc.M806025200.
- Faniello MC, Fregola A, Nisticò A; et al. Detection and functional analysis of an SNP in the promoter of the human ferritin H gene that modulates the gene expression.. Gene. 2006, 377: 1–5. PMID 16797877. doi:10.1016/j.gene.2006.02.034.
- Iwasaki K, Hailemariam K, Tsuji Y. PIAS3 interacts with ATF1 and regulates the human ferritin H gene through an antioxidant-responsive element.. J. Biol. Chem. 2007, 282 (31): 22335–43. PMC 2409283 . PMID 17565989. doi:10.1074/jbc.M701477200.
- MacKenzie EL, Tsuji Y. Elevated intracellular calcium increases ferritin H expression through an NFAT-independent post-transcriptional mechanism involving mRNA stabilization.. Biochem. J. 2008, 411 (1): 107–13. PMC 2702759 . PMID 18076382. doi:10.1042/BJ20071544.
- Fisher J, Devraj K, Ingram J; et al. Ferritin: a novel mechanism for delivery of iron to the brain and other organs.. Am. J. Physiol., Cell Physiol. 2007, 293 (2): C641–9. PMID 17459943. doi:10.1152/ajpcell.00599.2006.
- Campanella A, Rovelli E, Santambrogio P; et al. Mitochondrial ferritin limits oxidative damage regulating mitochondrial iron availability: hypothesis for a protective role in Friedreich ataxia.. Hum. Mol. Genet. 2009, 18 (1): 1–11. PMID 18815198. doi:10.1093/hmg/ddn308.
- Bou-Abdallah F, Biasiotto G, Arosio P, Chasteen ND. The putative "nucleation site" in human H-chain ferritin is not required for mineralization of the iron core.. Biochemistry. 2004, 43 (14): 4332–7. PMID 15065877. doi:10.1021/bi0498813.
- Binning RC, Bacelo DE. Computational modeling of the dizinc-ferroxidase complex of human H ferritin: direct comparison of the density functional theory calculated and experimental structures.. J. Biol. Inorg. Chem. 2009, 14 (8): 1199–208. PMID 19585161. doi:10.1007/s00775-009-0563-z.
- MacKenzie EL, Ray PD, Tsuji Y. Role and regulation of ferritin H in rotenone-mediated mitochondrial oxidative stress.. Free Radic. Biol. Med. 2008, 44 (9): 1762–71. PMC 2682214 . PMID 18325346. doi:10.1016/j.freeradbiomed.2008.01.031.
- Bou-Abdallah F, Santambrogio P, Levi S; et al. Unique iron binding and oxidation properties of human mitochondrial ferritin: a comparative analysis with Human H-chain ferritin.. J. Mol. Biol. 2005, 347 (3): 543–54. PMID 15755449. doi:10.1016/j.jmb.2005.01.007.
- Faniello MC, Di Sanzo M, Quaresima B; et al. p53-mediated downregulation of H ferritin promoter transcriptional efficiency via NF-Y.. Int. J. Biochem. Cell Biol. 2008, 40 (10): 2110–9. PMID 18372207. doi:10.1016/j.biocel.2008.02.010.
- Snyder AM, Wang X, Patton SM; et al. Mitochondrial ferritin in the substantia nigra in restless legs syndrome.. J. Neuropathol. Exp. Neurol. 2009, 68 (11): 1193–9. PMC 3024883 . PMID 19816198. doi:10.1097/NEN.0b013e3181bdc44f.